Scientists at the Babraham Institute, together with collaborators in the USA, have made a breakthrough in understanding how axons self-destruct in injury, ageing and disease. Axons are the long slender ‘wires’ projecting from nerve cells that communicate messages around the body. By unravelling the factors governing axon longevity, this work — supported in the UK by the Biotechnology and Biological Sciences Research Council (BBSRC) and Alzheimer’s Research UK — will increase understanding of both the normal ageing process in nerves and degenerative mechanisms widespread in disease. This breakthrough paves the way for research into new therapies to tackle axon loss in ageing-related conditions like Alzheimer’s Disease.

We lose axons in normal ageing and in neurodegenerative disease but the factors driving this, and whether the mechanisms are related, have until recently remained elusive. This research, reported in Science Express, pinpoints a protein called Sarm1 as having a pivotal role in axon degeneration. Sarm1 was originally thought to play a role in the defence of cells against viruses but in an unexpected twist, US collaborators Marc Freeman and colleagues at the University of Massachusetts Medical School found a similar protein in fruit flies that was needed for axons to die. Joint work with Dr Michael Coleman’s team at the Babraham Institute then investigated Sarm1 in mice to confirm this role in mammals. Axons in mice with normal levels of Sarm1 degenerated within hours of injury. Those without Sarm1 survived for over two weeks.

Dr Coleman said, “We’ve already learned a lot about axon degeneration by studying a protein that preserves axons. The problem has been how to apply this in humans – delivering a new protein into a complex nervous system would be extremely challenging. What’s so exciting about this development is that the new protein has to be blocked to protect axons. Inhibiting proteins is the kind of thing that the Pharma industry is particularly good at.” In Alzheimer’s disease, axons begin to deteriorate at an early stage, and finding ways of keeping them intact to keep brain cells communicating is a key goal for researchers.

Dr Eric Karran, Director of Research at Alzheimer’s Research UK, said, “We’re pleased to have supported this study, which has revealed a fundamental mechanism involved in axonal degeneration. More work is still needed to build on this progress and to help determine how the mechanism might be manipulated in the search for treatments for diseases where axonal damage is an important component. Alzheimer’s is the most common cause of dementia, which affects 820,000 people in the UK, and we urgently need to find new treatments if we are to tackle this growing crisis – that means investing in studies like this.”

The team now want to discover whether Sarm1 plays a role in Alzheimer’s disease, and whether drugs developed to target the protein could keep axons working for longer as the disease takes hold, potentially helping delay the onset of symptoms. It’s also hoped that a better understanding of Sarm1’s functions could open up new avenues for protecting against the loss of axons as part of the normal ageing process. Crucially, the researchers suggest that simply preserving axons during normal ageing could also benefit people with Alzheimer’s, by providing extra ‘cognitive reserve’ and helping the brain to resist damage caused by the disease.

Professor Michael Wakelam, Director of The Babraham Institute, which receives strategic funding from the BBSRC, said, “In an ageing population, it is vital to understand the process of normal ageing and to ensure that this new knowledge is applied to age-related disease. These exciting results are important for both. Babraham’s research supported by BBSRC has a focus on understanding healthy ageing and the Institute’s role in this study shows how we can maximise the impact of this fundamental work by partnering with charities such as Alzheimer’s Research UK”.

About the Babraham Institute:
The Babraham Institute undertakes world-class life sciences research to generate new knowledge of biological mechanisms underpinning ageing, development and the maintenance of health. Our research focuses on cellular signalling, gene regulation and the impact of epigenetic regulation at different stages of life. By determining how the body reacts to dietary and environmental stimuli and manages microbial and viral interactions, we aim to improve wellbeing and support healthier ageing. The Institute is strategically funded by the Biotechnology and Biological Sciences Research Council (BBSRC), part of UK Research and Innovation, through an Institute Core Capability Grant and also receives funding from other UK research councils, charitable foundations, the EU and medical charities.

The Biotechnology and Biological Sciences Research Council (BBSRC) is the UK funding agency for research in the life sciences. Sponsored by Government, BBSRC annually invests around £450 million in a wide range of research that makes a significant contribution to the quality of life for UK citizens and supports a number of important industrial stakeholders including the agriculture, food, chemical, health and well-being and pharmaceutical sectors. BBSRC carries out its mission by funding internationally competitive research, providing training in the biosciences, fostering opportunities for knowledge transfer and innovation and promoting interaction with the public and other stakeholders on issues of scientific interest in universities, centres and institutes.

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